The M9 is the standard pistol for the USMC. It is the starting pistol in all of the USMC missions except "Shock and Awe", where the player uses a M1911 as the starting pistol. Most enemies use the M9 as their sidearm, the exception being the Desert Eagle-wielding soldier in "Crew Expendable". It is very common in the majority of levels. The levels in which it cannot be obtained are "F.N.G.", "The Coup", "Aftermath", and "Death From Above". It is statistically the best pistol in single player, because of its virtually nonexistent recoil, high capacity, and decent power, but it really does not matter due to the abundance of enemy weapons available to pick up. It can be also seen holstered by Gaz and Price in all of the missions they appear in except from "F.N.G.", "Crew Expandable", "All Ghillied Up" and "One Shot, One Kill" although they never use it and always use a silenced USP. 45 as their secondaries.

If the player carries an MP5 or a Mini-Uzi, and uses an M9 as their sidearm, all maximum ammo for both weapons are combined, effectively increasing their ammunition count.

The M9 kills in 3-5 shots depending on the distance. Stopping Power improves this to 2-4 shot kills. Depending on range, head shots decrease the number of bullets needed to kill by one. The M9 has the highest magazine capacity of all the pistols in multiplayer as well as having the lowest recoil. It has the shortest range, but its larger capacity and better hipfire accuracy while moving balance it out, and at close range, the M9 is just as powerful as the USP .45 and M1911 .45. Outside of this, however, the M9 is significantly weaker than its counterparts. This makes the M9 a poorer choice on maps with open sidelines, where targets are often outside of its range.
The M9 shares ammo with the MP5 and Mini-Uzi; equipping it together with these weapons lessens the need for Bandolier as it increases total starting ammunition for the primary weapon. If Bandolier is used, the player can carry 270 rounds (with the MP5) or 282 (with the Mini-Uzi).

The M9 is available in the Assault and Demolitions default classes, and with a Silencer in the Sniper default class.

If the player is not carrying a pistol when falling into Last Stand, an M9 with no attachments will automatically be given to the player to use.

In Modern Warfare: Remastered, the M9 appears as the 6th weapon in Gun Game.

The M9 appears in Old School Mode as the default secondary, with 30 rounds in the magazine and 45 rounds of reserve ammunition. The only method of obtaining this weapon is upon spawn or from a dead player.

In the Nintendo DS version of Call of Duty 4: Modern Warfare, the M9 appears as the only sidearm in the game. It is almost identical to its console and PC counterpart in appearance, but is much weaker than on the consoles, taking a maximum of 20 shots to the limbs for one kill at range. Like all other weapons in the game, it has no idle sway and no reload animation. The lack of a fire-cap makes this weapon automatic, with its rate of fire varying by mode, but always remaining very low.

When firing from the hip, the M9 appears to have a very high recoil. However, it has no recoil when sighted.

The M9 now has higher minimum damage, better bullet penetration, much better range, but a lower fire rate than its counterpart in Call of Duty 4: Modern Warfare, but is unlocked at Level 46, and suffers from higher recoil. It is the default handgun used for Last Stand when the player is using a secondary weapon that is not a handgun or the M93 Raffica, regardless of the player's level, and does not have any attachments.

Even while using ADS, the M9 recoils side-to-side and upwards. Because of this, it is nearly impossible to fire accurately at range, unless it is fired slowly, letting the recoil settle. However, at close range, the player can fire as quickly as possible without any worry. When the M9 is used with the Tactical Knife attachment, the sights will become misaligned and the actual shot will land slightly to the right of the sights. Using the Tactical Knife on the M9 increases visual recoil as well.

The M9 no longer retains its advantage over the USP .45 with higher hipfire accuracy, as both are the same, nor is it relatively accurate compared to the other handguns. The USP .45 has a slightly longer 3 hit kill range, with the disadvantage of a three round smaller magazine.

The M9 is subject to numerous glitches. The weapon's Expert challenges stay locked until the Desert Eagle is unlocked at level 62. Due to another glitch, the Silencer does not work on the M9. Players will still appear on the enemy radar when firing a silenced M9. It shares this problem with the MG4 and the M240. This glitch has been in the game since launch and has never been fixed. The only effective suppressed pistol, therefore, is the USP .45. Also, when used with Akimbo, the player's view will rock oddly from side to side while running.

The M9 reappears in Call of Duty: Modern Warfare: Mobilized as the one of the two sidearms available in-game. The M9 is significantly different from the console versions, as it has much higher damage, increased recoil, and is nickel-plated. In singleplayer, the M9 is available in four missions: "Training", "Distant Information", "Wrecking Crew", and "Interception". It is basically the same as the USP .45, but it is used more often, and sports a unique color scheme. It is not capable of one shot kills (excepting headshots), but can kill in two-three shots at any range.

In multiplayer, the M9 is the default side arm for the Insurgency faction. As in singleplayer, there is no difference between the USP .45 and the M9. Because of this, it shares the same characteristics as the USP .45, such as LMG-like hipfire accuracy when moving, near perfect hipfire accuracy when standing still, perfect hipfire accuracy when crouched, and moderate power.

In Call of Duty: Modern Warfare 3, the M9 is only available in the campaign. While it doesn't make a major appearance like in other Modern Warfare games, it is drawn from the holsters of random Rangers and Marine tankers in the campaign level "Goalpost" after running out of ammunition or in the middle of reloading their primary weapon; it can be picked up off the bodies of dead NPCs and used by the player in that level. It can also be seen in the holster of the driver of the crashed Humvee at the start of "Black Tuesday".

The M9 can be found with Akimbo as well. However, this version is bugged, as none of the two pistols can be fired, even though they have loaded rounds and can be reloaded after being picked up.

In the campaign the M9 is the starting weapon for some missions and can be rarely found on ammunition crates. It is never seen in use by enemy forces or friendly forces at all. In the mission "Oil, Fire, and Ice", two M9s can be seen on the same ammunition crate. When one of these two M9s are picked up, for some strange reason the other M9 can still be picked up as well. One of the M9s when picked up will show the player having the Alaskan National Guard first-person model while the other M9 when picked up will show the player having the normal National Guard first-person model.

Soldiers can sometimes be seen with holstered M9s in the campaign levels set in 2025, particularly Section, Harper and Salazar. This weapon is not obtainable during gameplay, and when Harper or Salazar draw their pistol, it turns into a Five-seven.

The M9A1 is part of Logan's starting loadout in the missions "Brave New World", "Homecoming", and "Birds of Prey". It has a rather restricted firecap compared to the other handguns (and compared to its multiplayer counterpart). Hesh also uses it sometimes as his secondary weapon. The only mission where the Federation troops use it as their secondary weapon is "Brave New World", as it is replaced by the P226 and the MP-443 Grach in the later levels, though one Federation tank operator actually attempts to use a M9A1 against Elias Walker in "Legends Never Die". Finally, some M9A1s can be obtained from a weapons cache in "Sin City", including silenced ones.

The M9A1 the first handgun unlocked. It has a decent sized magazine at 12 rounds, the fastest reload for handguns, a decent fire rate, and the highest long range damage. Compared to the most similar pistol, the P226, it exchanges range for long range damage. Although the two shot kill range does not differ greatly from that of the P226, it greatly differs with its three shot kill range. Anything after its three shot kill range will take four shots to kill, the highest of the three semi-automatic handguns. This makes it a great back up for lower ranged weapons like the SMGs.Hipfiring isn't recommended

Extended Mags allows for the M9A1 to hold 18 rounds instead of 12 and gives it an extra 50% reserve ammo. This can help to engage more enemies reduce the frequency of reloads. The Silencer isn't a bad choice either, as the difference to the two shot kill range is minimal and the four shot kill at longer distances prevents it from being too heavily affected at a distance. Armor Piercing is another good attachment, allowing for better penetration through walls and entirely negating the effects of Ballistic Vests (it also helps with destroying enemy scorestreaks). The Muzzle Brake will increase the range of the M9A1, allowing for it to achieve a two shot and three shot kill out to farther ranges. The Flash Suppressor should be avoided on the M9A1, as the slow semi-automatic fire will limit muzzle flash.

The M9A1 appears in Extinction as a three-round burst firing weapon, rather than the semi-automatic mode as seen in the campaign and multiplayer. It has slightly less damage than the P226 and has less range as well. However, it has the largest magazine of the pistols in Extinction and a good fire rate within the burst, making it good at a close range where the recoil won't send the burst above the enemy Cryptid.